Aneustat (OMN54) has aerobic glycolysis‐inhibitory activity and also immunomodulatory activity as indicated by a first‐generation PDX prostate cancer model

Abstract

Aneustat (OMN54) is a multivalent, botanical anticancer candidate therapeutic. A recent Phase‐I clinical trial has indicated that it is well tolerated by patients and has immunomodulatory activity. In our study, using in vitro and in vivo prostate cancer models, we investigated Aneustat with regard to effects on (i) cancer‐generated immunosuppression based on aerobic glycolysis leading to acidification of the tumor microenvironment, and (ii) immune‐related processes such as macrophage differentiation and shifts in the intratumoral levels of host immune cells. Aneustat markedly reduced glucose consumption, lactic acid secretion, glycolysis‐related gene expressions and proliferation of human LNCaP prostate cancer cells. In addition, Aneustat induced differentiation of RAW264.7 macrophages to the M1 anticancer phenotype. Treatment of LNCaP xenografts and first‐generation patient‐derived prostate cancer tissue xenografts with Aneustat in both cases led to a marked shift in intratumoral host (mouse/patient) immune cell levels: a higher ratio of cytotoxic CD8+ T/Treg cells, higher numbers of NK cells, lower numbers of Treg cells and MDSCs, i.e. changes favoring the host anticancer immune response. Taken together, the data indicate that Aneustat has immunomodulatory activity based on inhibition of aerobic glycolysis which in patients may lead to reduction of cancer‐induced immunosuppression. Furthermore, first‐generation patient‐derived cancer tissue xenograft models may be used for screening compounds for immunomodulatory activity.

Characterization of myeloid signature genes for predicting prognosis and immune landscape in Ewing sarcoma

“…Functional enrichment analysis showed that DEGs in the high‐ and low‐risk groups were highly relevant to immune‐related pathways. The immune system has a dual role in tumor development, as it can recognize and eradicate tumor cells on the one hand, while promoting tumor growth by establishing a favorable microenvironment on the other hand 36 . Moreover, the results of the GSEA analysis also support these findings.…”

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